Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETA and ETB receptors

Reactive oxygen species (ROS) play important roles in renal vasoconstrictor responses to acute and chronic stimulation by angiotensin II and norepinephrine, as well as in long-term effects of endothelin-1 (ET-1). Little is known about participation of ROS in acute vasoconstriction produced by ET-1. We tested the influence of NAD(P) H oxidase inhibition by apocynin [4 mg center dot kg(-1) center dot min(-1), infused into the renal artery (ira)] on ETA and ETB receptor signaling in the renal microcirculation. Both receptors were stimulated by ET-1, ETA receptors by ET-1 during ETB antagonist BQ-788, and ETB by ETB agonist sarafotoxin 6C. ET-1 (1.5 pmol injected ira) reduced renal blood flow (RBF) 17 +/- 4%. Apocynin raised baseline RBF (+ 10 +/- 1%, P < 0.001) and attenuated the ET-1 response to 10 +/- 2%, i.e., 35 +/- 9% inhibition (P < 0.05). Apocynin reduced ETA-induced vasoconstriction by 42 +/- 12% (P < 0.05) and that of ETB stimulation by 50 +/- 8% (P < 0.001). During nitric oxide (NO) synthase inhibition (N-omega-nitro-L-arginine methyl ester), apocynin blunted ETA-mediated vasoconstriction by 60 +/- 8% (P < 0.01), whereas its effect on the ETB response (by 87 +/- 8%, P < 0.001) was even larger without than with NO present (P < 0.05). The cell-permeable superoxide dismutase mimetic tempol (5 mg center dot kg(-1) center dot min(-1) ira), which reduces O-2(-) and may elevate H2O2, attenuated ET-1 responses similar to apocynin (by 38 +/- 6%, P < 0.01). We conclude that ROS, O-2(-) rather than H2O2, contribute substantially to acute renal vasoconstriction elicited by both ETA and ETB receptors and to basal renal vasomotor tone in vivo. This physiological constrictor action of ROS does not depend on scavenging of NO. In contrast, scavenging of O-2(-) by NO seems to be more important during ETB stimulation.